Design, Synthesis, and Antimicrobial Evaluation of Novel Sulfonamide Modified with Azoles

Background Sulfonamide, imidazole, and triazole chemical nuclei possess good antimicrobial potential.Aims This study aimed to amalgamate sulfonamide, imidazole, and triazole moieties in a single molecular framework with the intent of improving their antimicrobial activities.Objective The objective of this study was the synthesis of conjugates containing sulfonamide and azole moieties along with in vitro and in silico evaluation as antimicrobial candidates.Method A series of sulfonamide-modified azoles (7a-r) was synthesized by multicomponent condensation of 1,2-dicarbonyl compounds, ammonium acetate and aryl-substituted aldehydes in glacial acetic acid. The structure of synthesized molecules was elucidated with the help of various spectroscopic techniques, such as FTIR, NMR, and HRMS. The target molecules were tested for in vitro antimicrobial potency against four bacterial strains and two fungal strains.Result Molecules 7c (MIC 0.0188 mu mol/mL), 7f (MIC 0.0170 mu mol/mL) and 7i (MIC 0.0181 mu mol/mL) were most active against S. aureus and C. albicans. Against E. coli, molecules 7d (MIC 0.0179 mu mol/mL), 7f (MIC 0.0170 mu mol/mL) and 7i (MIC 0.0181 mu mol/mL) were found to be highly active. Moreover, the binding conformations were investigated by in-silico molecular docking, and QTAIM (Quantitative theory of atoms in the molecule) analysis was also performed. Molecular properties, such as the heat of formation, HOMO energy, LUMO energy and COSMO volume, were found to be in direct correlation with the antimicrobial potency of molecules 7c, 7f and 7i against S. aureus and C. albicans.Conclusion All the synthesized molecules were more potent than clinically approved sulfonamides, namely sulfadiazine and sulfabenzamide.